Integrative meta-analysis of the OSCC microbiome: from niche-specific heterogeneity to universal network and functional signatures.

BACKGROUND: While the association between oral squamous cell carcinoma (OSCC) and microbial dysbiosis is well-established, high inter-study heterogeneity has historically hindered the identification of universal biomarkers. OBJECTIVE: To explore the profound influence of anatomical ecological niches on microbial profiles while identifying shared oncogenic signatures across diverse populations. DESIGN: An integrative meta-analysis of independent OSCC microbiome cohorts was conducted. RESULTS: Our results demonstrate that microbial community composition is predominantly driven by the sampling site rather than the disease state alone, with tissue-derived samples forming a distinct ecological cluster. Despite this site-specific dominance, a consistent core of anaerobic pathogens-including Fusobacterium, Capnocytophaga, and Treponema was significantly enriched in OSCC across multiple datasets. Network-based analysis identified Fusobacterium as top driver of microbial community restructuring. Diagnostically, saliva-based models achieved superior accuracy compared to tissue and mucosal models, suggesting that saliva serves as an integrative reservoir for oral pathological changes. Functional profiling further revealed a significant functional convergence toward pathways essential for rapid bacterial proliferation and environmental adaptation, such as ribosome biogenesis, DNA replication, and flagellar assembly. CONCLUSIONS: These findings emphasize the necessity of standardizing sampling protocols and provide a robust scientific basis for non-invasive, saliva-based precision diagnostic strategies for OSCC.